The control of cell proliferation of stem cell population of cells in the germline is a fundamental property of biological systems that requires an exquisite level of regulation to ensure normal reproductive function. Sexual reproduction of multicellular organisms depends on a number of germ cells that decide whether to differentiate or to continue to divide (meiosis vs. mitosis). The regulation of cell proliferation may require a number of external signals, such as nutrition or stress conditions, which may impact on the regulation of the competence to proliferate, a poorly understood aspect of cell fate specification, as well as the regulation of mitosis and the control of the cell-cycle. The C. elegans germline is a valuable model to study the genetic, developmental, and environmental control of germ cell proliferation. Because of the fundamental nature of growth control, its regulation is likely to be conserved through evolution, enabling the use of simple, genetically tractable organisms as model systems. A conserved GLP-1/Notch signaling pathway controls the cell fate decision to retain proliferative competence or to differentiate by entering meiosis. In this study, we will elucidate the role of autophagy and other endocytic pathways on GLP-1/Notch signaling. Specifically, our proposal aims to: (1) define the role of autophagy and retromer activity during C. elegans development, specifically in the regulation of the glp-1/Notch signaling in the development of the germline, and to (2) elucidate the role of endocytic genes in the formation of an autophagosome, in dauer development and during germline development. These studies are significant because they will advance our understanding of the mechanisms by which autophagy functions in the development of a multicellular organism, and in the control of cell proliferation. They will be informative regarding both the tissues that require autophagy in development and the proteins involved in the signaling pathway. Our laboratory is uniquely positioned to pursue this project with our expertise in C. elegans genetics and the study of autophagy. PUBLIC HEALTH RELEVANCE: This study aims to explore the role of autophagy - a cellular pathway by which cytoplasmic components are recycled - in germline development by examining links between autophagy, retromer function and the Notch/GLP-1 signaling pathway.